Chemokines and Chemokine Receptors: Orchestrating Tumor Metastasization

doi:10.3390/ijms20010096

Review

. 2018 Dec 27;20(1):96.

doi: 10.3390/ijms20010096.

Chemokines and Chemokine Receptors: Orchestrating Tumor Metastasization

Elisabetta Marcuzzi^{1

2}, Roberta Angioni^{3

4}, Barbara Molon⁵, Bianca Calì^{6

7

8}

Affiliations

¹ Department of Biomedical Sciences, University of Padova, 35131 Padova, Italy. elisabetta.marcuzzi@phd.unipd.it.
² Fondazione Istituto di Ricerca Pediatrica Città della Speranza, 35127 Padova, Italy. elisabetta.marcuzzi@phd.unipd.it.
³ Department of Biomedical Sciences, University of Padova, 35131 Padova, Italy. roberta.angioni@studenti.unipd.it.
⁴ Fondazione Istituto di Ricerca Pediatrica Città della Speranza, 35127 Padova, Italy. roberta.angioni@studenti.unipd.it.
⁵ Department of Biomedical Sciences, University of Padova, 35131 Padova, Italy. barbara.molon@unipd.it.
⁶ Department of Biomedical Sciences, University of Padova, 35131 Padova, Italy. bianca.cali@unipd.it.
⁷ Fondazione Istituto di Ricerca Pediatrica Città della Speranza, 35127 Padova, Italy. bianca.cali@unipd.it.
⁸ Institut Curie, 75005 Paris, France. bianca.cali@unipd.it.

PMID: 30591657
PMCID: PMC6337330
DOI: 10.3390/ijms20010096

Review

Chemokines and Chemokine Receptors: Orchestrating Tumor Metastasization

Elisabetta Marcuzzi et al. Int J Mol Sci. 2018.

. 2018 Dec 27;20(1):96.

doi: 10.3390/ijms20010096.

Authors

Elisabetta Marcuzzi^{1

2}, Roberta Angioni^{3

4}, Barbara Molon⁵, Bianca Calì^{6

7

8}

Affiliations

¹ Department of Biomedical Sciences, University of Padova, 35131 Padova, Italy. elisabetta.marcuzzi@phd.unipd.it.
² Fondazione Istituto di Ricerca Pediatrica Città della Speranza, 35127 Padova, Italy. elisabetta.marcuzzi@phd.unipd.it.
³ Department of Biomedical Sciences, University of Padova, 35131 Padova, Italy. roberta.angioni@studenti.unipd.it.
⁴ Fondazione Istituto di Ricerca Pediatrica Città della Speranza, 35127 Padova, Italy. roberta.angioni@studenti.unipd.it.
⁵ Department of Biomedical Sciences, University of Padova, 35131 Padova, Italy. barbara.molon@unipd.it.
⁶ Department of Biomedical Sciences, University of Padova, 35131 Padova, Italy. bianca.cali@unipd.it.
⁷ Fondazione Istituto di Ricerca Pediatrica Città della Speranza, 35127 Padova, Italy. bianca.cali@unipd.it.
⁸ Institut Curie, 75005 Paris, France. bianca.cali@unipd.it.

PMID: 30591657
PMCID: PMC6337330
DOI: 10.3390/ijms20010096

Erratum in

Correction: Marcuzzi, E., et al. Chemokines and Chemokine Receptors: Orchestrating Tumor Metastasization. Int. J. Mol. Sci. 2019, 20, 96.
Marcuzzi E, Angioni R, Molon B, Calì B. Marcuzzi E, et al. Int J Mol Sci. 2019 May 29;20(11):2651. doi: 10.3390/ijms20112651. Int J Mol Sci. 2019. PMID: 31146450 Free PMC article.

Abstract

Metastasis still represents the primary cause of cancer morbidity and mortality worldwide. Chemokine signalling contributes to the overall process of cancer growth and metastasis, and their expression in both primary tumors and metastatic lesions correlate with prognosis. Chemokines promote tumor metastasization by directly supporting cancer cell survival and invasion, angiogenesis, and by indirectly shaping the pre-metastatic niches and antitumor immunity. Here, we will focus on the relevant chemokine/chemokine receptor axes that have been described to drive the metastatic process. We elaborate on their role in the regulation of tumor angiogenesis and immune cell recruitment at both the primary tumor lesions and the pre-metastatic foci. Furthermore, we also discuss the advantages and limits of current pharmacological strategies developed to target chemokine networks for cancer therapy.

Keywords: angiogenesis; cancer; chemokine; metastasis; tumor immunity.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

**Figure 1**
Chemokines contribute to the overall process of tumor metastasis. (a) Chemokines promote proliferation and survival of tumor cells at the primary lesion in an autocrine fashion. (b) The balance between angiostatic and angiogenic chemokines secreted by stromal cells, immune cells and platelets regulates tumor associated-angiogenesis by supporting endothelial cell proliferation and sprouting, and promoting remodelling of the surrounding extracellular matrix. (c) Chemokine gradients shape the tumor microenvironment both in the primary sites and pre-metastatic niches by recruiting different types of immune cells. Whilst T cells and NK cells have an antitumoral effect, T_reg cells, tumor associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs) and tolerogenic dendritic cells (DCs) inhibit antitumor immunity and support the metastatic process. (d) Myeloid immune cells accumulating at the pre-metastatic niches, in turn, secrete chemokines that promote angiogenesis and tumor invasion.

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References

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1. Sarvaiya P.J., Guo D., Ulasov I., Gabikian P., Lesniak M.S. Chemokines in tumor progression and metastasis. Oncotarget. 2013;4:2171–2185. doi: 10.18632/oncotarget.1426. - DOI - PMC - PubMed
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[1] Steeg P.S. Targeting metastasis. Nat. Rev. Cancer. 2016;16:201–218. doi: 10.1038/nrc.2016.25. - DOI - PMC - PubMed

[2] Steeg P.S. Targeting metastasis. Nat. Rev. Cancer. 2016;16:201–218. doi: 10.1038/nrc.2016.25. - DOI - PMC - PubMed

[3] Sarvaiya P.J., Guo D., Ulasov I., Gabikian P., Lesniak M.S. Chemokines in tumor progression and metastasis. Oncotarget. 2013;4:2171–2185. doi: 10.18632/oncotarget.1426. - DOI - PMC - PubMed

[4] Sarvaiya P.J., Guo D., Ulasov I., Gabikian P., Lesniak M.S. Chemokines in tumor progression and metastasis. Oncotarget. 2013;4:2171–2185. doi: 10.18632/oncotarget.1426. - DOI - PMC - PubMed

[5] Zlotnik A., Burkhardt A.M., Homey B. Homeostatic chemokine receptors and organ-specific metastasis. Nat. Rev. Immunol. 2011;11:597–606. doi: 10.1038/nri3049. - DOI - PubMed

[6] Zlotnik A., Burkhardt A.M., Homey B. Homeostatic chemokine receptors and organ-specific metastasis. Nat. Rev. Immunol. 2011;11:597–606. doi: 10.1038/nri3049. - DOI - PubMed

[7] Muller A., Homey B., Soto H., Ge N., Catron D., Buchanan M.E., McClanahan T., Murphy E., Yuan W., Wagner S.N., et al. Involvement of chemokine receptors in breast cancer metastasis. Nature. 2001;410:50–56. doi: 10.1038/35065016. - DOI - PubMed

[8] Muller A., Homey B., Soto H., Ge N., Catron D., Buchanan M.E., McClanahan T., Murphy E., Yuan W., Wagner S.N., et al. Involvement of chemokine receptors in breast cancer metastasis. Nature. 2001;410:50–56. doi: 10.1038/35065016. - DOI - PubMed

[9] Liu Y., Cao X. Characteristics and Significance of the Pre-metastatic Niche. Cancer Cell. 2016;30:668–681. doi: 10.1016/j.ccell.2016.09.011. - DOI - PubMed

[10] Liu Y., Cao X. Characteristics and Significance of the Pre-metastatic Niche. Cancer Cell. 2016;30:668–681. doi: 10.1016/j.ccell.2016.09.011. - DOI - PubMed

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Chemokines and Chemokine Receptors: Orchestrating Tumor Metastasization

Affiliations

Chemokines and Chemokine Receptors: Orchestrating Tumor Metastasization

Authors

Affiliations

Erratum in

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Conflict of interest statement

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